Protective Effect Of Sodium Butyrate On The Neonatal Mouse Model Of Necrotizing Enterocolitis

Objective:To investigate the protective effect of sodium butyrate on the neonatal neonatal mouse model of necrotizing enterocolitis and analyze its possible mechanism.Methods:Sixty C57BL/6 3 day newborn mice were divided into two groups according to the random number table method.Sixty c57bl/6 neonatal mice were randomly divided into two groups(n=30): PBS group and butyric acid group.On the third day after birth,PBS and butyrate mice were intragastrically administered with PBS and butyrate solution,respectively,once a day for 7 days,followed by hypoxia + cold stimulation + artificial feeding for 3 consecutive days;The NEC model was established twice a day and the newborn mice were sacrificed overnight.To observe whether the intestinal tissue has bleeding,gas,necrosis,etc.HE staining and double-blind pathological score was used to observe the pathological changes of ileocecal intestinal tissue.The mRNA expression of IL-6,TNF-a,TGF-?1and IL-10 were tested by quantitative real-time PCR.The levels of IL-10,TGF-?1 in intestine tissues were evaluated by using ELISA.Flow cytometry was used to analyze the ratio of regulatory T cells(Treg)on CD4+ T cells in both groups.Results:Body weight(4.50±0.42g)in butyrate group was significantly higher than that in PBS group(4.16±0.60 g,P<0.05);butyrate group survival was 76.34%,PBS group survival was 67.95%(P>0.05).The pathological damage score of intestinal tissue showed that the median score of intestinal injury in butyrate group was 1.33(1.33-1.67),which was significantly lower than PBS group [2.00(1.67-2.25),P<0.05].Compared with the PBS group,the body weight of neonates mice in the butyric acid group decreased more slowly,the mortality rate during modeling was relatively low,and the pathological damage of intestinal mucosa was relatively reduced.IL-6,TNF-? mRNA expression of intestinal tissue in butyrate group were lower(P<0.05);IL-10,TGF-?1 mRNA expression of intestinal tissue in butyrate group were higher(P<0.05);intestinal tissue ELISA results showed that the expression of IL-10 and TGF-?1 in butyrate group were higher(P<0.05);Regulatory T cells(Treg)of CD4+ T cells in the intestine of the butyric acid group were higher than those in PBS(P<0.05).Conclusion:Butyric acid plays a protective role in the intestinal injury of neonatal neonatal mouse model of necrotizing enterocolitis.The possible mechanism is that butyrate can down-regulate the expression of cytokines IL-6 and TNF-?,up-regulate the expression of cytokines IL-10 and TGF-?1 and promote the differentiation of T cells into Treg cells.